ANCA_vasculitis - Tuesday Clinical Case Conference...

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Unformatted text preview: Tuesday Clinical Case Conference Conference Zae Kim Therapy of ANCA-Associated Small Vessel Vasculitis Small Introduction Introduction • Best known induction therapy • Cyclophosphamide / Steroid • Search for alternative induction agent • NORAM • Minimizing the use of CYC • Oral vs IV CyA - CYCLOPS • CYCAZAREM (cyclophosphamide vs azathioprine CYCAZAREM for early remission phase of vasculitis) for Cyclophosphamide / Steroid Cyclophosphamide Mainstay of treatment Mainstay for both MPA and WG since 1980s since High rate of remission Significant morbidity Hemorragic cystitis Bladder cancer Myelodysplasia Infertility infection What are the approaches to maintaining remission without CYC? maintaining • NORAM NORAM Randomized Trial of Cya vs Mtx for Induction of Remissioi nin early systemic ANCAAV_de groot_ArthRheu_2005 NORAM – remission at 6 months NORAM Randomized Trial of Cya vs Mtx for Induction of Remissioi nin early systemic ANCAAV_de groot_ArthRheu_2005 NORAM - relapses NORAM Randomized Trial of Cya vs Mtx for Induction of Remissioi nin early systemic ANCAAV_de groot_ArthRheu_2005 Minimizing exposure to CYC Minimizing • Minimizing the use of CYC • Induction • Oral vs IV CyA - CYCLOPS • Maintenance • CYCAZAREM (cyclophosphamide vs azathioprine CYCAZAREM for early remission phase of vasculitis) for • MMF? Which is better: Oral or IV CYC? Which • Guillevin L et al, Arthritis Rheum, 1997 • RCT of patients with WG Group A (CYC IV) Group n = 27 27 Group B (CYC PO) Group n = 23 23 Initial remission 89% 78% Infectious side Infectious effect effect 41% 70% 70% Relapse 60% (p < 0.05) (p 13% 13% (p = 0.02) (p CYC: oral vs pulse IV, meta analysis analysis • Meta-analysis Meta-analysis • • • 11 non-randomized studies 11 N = 202 patients 202 Pulse vs daily oral Cya • • • • No difference in death / ESRD / remission More relapses OR 1.79* (CI 0.85-3.75) Less infections RR 0.45 Lower dose 17 g vs. 35 g Lower 17 *not statistically significant K de Groot et al. Nephrol Dial Transplant 2001; 16:2018­27 CYC: Is IV pulse as effective as PO CYC? CYC? CYCLOPS – Time to remission CYCLOPS Cyclops – Time to relapse Cyclops Minimizing exposure to CYC Minimizing • Minimizing the use of CYC • Induction • Oral vs IV CyA - CYCLOPS • Maintenance • CYCAZAREM (cyclophosphamide vs azathioprine CYCAZAREM for early remission phase of vasculitis) for • MMF? CYCAZAREM trial CYCAZAREM Jayne et al, NEJM, 349;1, 2003 CYCAZAREM - remission CYCAZAREM Jayne et al, NEJM, 349;1, 2003 Time to first relapse Time Jayne et al, NEJM, 349;1, 2003 CYCAZAREM – renal recovery CYCAZAREM Jayne et al, NEJM, 349;1, 2003 CYCAZAREM - conclusion CYCAZAREM • No difference in relapse rate • • Only predictor of relapse was • • CTX (14%) vs AZA (15%) MPA (8%) vs WG (18%) No difference in serious adverse events Alternative to AZA as maintenance therapy therapy • MTx / Leflunomide • Metzler et al, Rheumatology 2007 • 55 patients with generalized WG • Study terminated early 2/2 Study • • • higher rate of relapse in MTx group higher high rate of adverse event in Leflunomide IMPROVE by EUVAS • MMF vs AZA Ongoing trials at EUVAS Ongoing • Length of long-term immunosuppressive therapy? • REMAIN REMAIN • llong-term low dose immunosuppression versus treatment ong-term withdrawal for renal vasculitis withdrawal Alternative induction agent? • MYCYC (Randomized clinical trial of MMF vs CYC for MYCYC remission induction in ANCA-AV) remission • RITUXVAS • MMF as remission agent? • IMPROVE • Clearance of nasal carriage of Staph Aureus Clearance with mupirocin in WG with • MUPIBAC ...
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This note was uploaded on 12/24/2011 for the course STEP 1 taught by Professor Dr.aslam during the Fall '11 term at Montgomery College.

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